Role of sulphuric acid, ammonia and galactic cosmic rays in atmospheric aerosol nucleation

Atmospheric aerosols exert an important influence on climate through their effects on stratiform cloud albedo and lifetime and the invigoration of convective storms. Model calculations suggest that almost half of the global cloud condensation nuclei in the atmospheric boundary layer may originate from the nucleation of aerosols from trace condensable vapours, although the sensitivity of the number of cloud condensation nuclei to changes of nucleation rate may be small. Despite extensive research, fundamental questions remain about the nucleation rate of sulphuric acid particles and the mechanisms responsible, including the roles of galactic cosmic rays and other chemical species such as ammonia. Here we present the first results from the CLOUD experiment at CERN. We find that atmospherically relevant ammonia mixing ratios of 100 parts per trillion by volume, or less, increase the nucleation rate of sulphuric acid particles more than 100-1,000-fold. Time-resolved molecular measurements reveal that nucleation proceeds by a base-stabilization mechanism involving the stepwise accretion of ammonia molecules. Ions increase the nucleation rate by an additional factor of between two and more than ten at ground-level galactic-cosmic-ray intensities, provided that the nucleation rate lies below the limiting ion-pair production rate. We find that ion-induced binary nucleation of H(2)SO(4)-H(2)O can occur in the mid-troposphere but is negligible in the boundary layer. However, even with the large enhancements in rate due to ammonia and ions, atmospheric concentrations of ammonia and sulphuric acid are insufficient to account for observed boundary-layer nucleation.     

Intra-brain microinjection of human mesenchymal stem cells decreases allodynia in neuropathic mice

Neuropathic pain is a very complex disease, involving several molecular pathways. Current available drugs are usually not acting on the several mechanisms underlying the generation and propagation of pain. We used spared nerve injury model of neuropathic pain to assess the possible use of human mesenchymal stem cells (hMSCs) as anti-neuropathic tool. Human MSCs were transplanted in the mouse lateral cerebral ventricle. Stem cells injection was performed 4 days after sciatic nerve surgery. Neuropathic mice were monitored 7, 10, 14, 17, and 21 days after surgery. hMSCs were able to reduce pain-like behaviors, such as mechanical allodynia and thermal hyperalgesia, once transplanted in cerebral ventricle. Anti-nociceptive effect was detectable from day 10 after surgery (6 days post cell injection). Human MSCs reduced the mRNA levels of the pro-inflammatory interleukin IL-1β mouse gene, as well as the neural β-galactosidase over-activation in prefrontal cortex of SNI mice. Transplanted hMSCs were able to reduce astrocytic and microglial cell activation.     

Metabolic syndrome as a risk factor for neurological disorders

The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin resistance, dyslipidemia and hypertension. At the molecular level, metabolic syndrome is accompanied not only by dysregulation in the expression of adipokines (cytokines and chemokines), but also by alterations in levels of leptin, a peptide hormone released by white adipose tissue. These changes modulate immune response and inflammation that lead to alterations in the hypothalamic ‘bodyweight/appetite/satiety set point,’ resulting in the initiation and development of metabolic syndrome. Metabolic syndrome is a risk factor for neurological disorders such as stroke, depression and Alzheimer’s disease. The molecular mechanism underlying the mirror relationship between metabolic syndrome and neurological disorders is not fully understood. However, it is becoming increasingly evident that all cellular and biochemical alterations observed in metabolic syndrome like impairment of endothelial cell function, abnormality in essential fatty acid metabolism and alterations in lipid mediators along with abnormal insulin/leptin signaling may represent a pathological bridge between metabolic syndrome and neurological disorders such as stroke, Alzheimer’s disease and depression. The purpose of this review is not only to describe the involvement of brain in the pathogenesis of metabolic syndrome, but also to link the pathogenesis of metabolic syndrome with neurochemical changes in stroke, Alzheimer’s disease and depression to a wider audience of neuroscientists with the hope that this discussion will initiate more studies on the relationship between metabolic syndrome and neurological disorders.     

Light on the structure of thromboxane A2 receptor heterodimers

The structure-based design of a mutant form of the thromboxane A(2) prostanoid receptor (TP) was instrumental in characterizing the structural determinants of the hetero-dimerization process of this G protein coupled receptor (GPCR). The results suggest that the hetero-dimeric complexes between the TPα and β isoforms are characterized by contacts between hydrophobic residues in helix 1 from both monomers. Functional characterization confirms that TPα-TPβ hetero-dimerization serves to regulate TPα function through agonist-induced internalization, with important implications in cardiovascular homeostasis. The integrated approach employed in this study can be adopted to gain structural and functional insights into the dimerization/oligomerization process of all GPCRs for which the structural model of the monomer can be achieved at reasonable atomic resolution.     

A Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration

Epithelial organs, including the lung, are known to possess regenerative abilities through activation of endogenous stem cell populations, but the molecular pathways regulating stem cell expansion and regeneration are not well understood. Here we show that Gata6 regulates the temporal appearance and number of bronchioalveolar stem cells (BASCs) in the lung, its absence in Gata6-null lung epithelium leading to the precocious appearance of BASCs and concurrent loss in epithelial differentiation. This expansion of BASCs was the result of a pronounced increase in canonical Wnt signaling in lung epithelium upon loss of Gata6. Expression of the noncanonical Wnt receptor Fzd2 was downregulated in Gata6 mutants and increased Fzd2 or decreased beta-catenin expression rescued, in part, the lung epithelial defects in Gata6 mutants. During lung epithelial regeneration, canonical Wnt signaling was activated in the niche containing BASCs and forced activation of Wnt signaling led to a large increase in BASC numbers. Moreover, Gata6 was required for proper lung epithelial regeneration, and postnatal loss of Gata6 led to increased BASC expansion and decreased differentiation. Together, these data demonstrate that Gata6-regulated Wnt signaling controls the balance between progenitor expansion and epithelial differentiation required for both lung development and regeneration.     

Institutional experience of PTH evaluation on fine-needle washing after aspiration biopsy to locate hyperfunctioning parathyroid tissue

Assaying parathyroid hormone (PTH) in the washing liquid after fine-needle aspiration biopsy (FNAB) seems to be a valid approach to locate parathyroid tissue. PTH-FNAB was evaluated in 47 patients with a clinical picture of primary hyperparathyroidism (PHP) and ultrasonography (US) suggestive of parathyroid lesion. The patients were subdivided into two groups on the basis of the absence or presence of US thyroid alterations. The result of PTH-FNAB was compared with those of cytology, scintigraphy and, in 24 patients, surgical outcome. PTH-FNAB samples with a value higher than that recorded in the serum and higher than our institutional cut-off were deemed to be probable samples of parathyroid tissue. Cytology proved diagnostic for benign thyroid lesions, non-diagnostic for thyroid lesions, hyperplastic parathyroid tissue, undetermined or malignant thyroid lesions and other lesions in 45%, 30%, 17%, 4%, and 4% of cases, respectively. In 47% of cases, PTH-FNAB indicated that the sample had been taken in parathyroid tissue. In patients without US alterations, the diagnostic accuracy of PTH-FNAB was greater than that of scintigraphy. After surgery, comparison between the results of PTH-FNAB and scintigraphy, in terms of positive predictive value (PPV), revealed the superiority of PTH-FNAB; PPV was 94% for FNAB and 71% for scintigraphy, while sensitivity was 83% and 69%, respectively. PTH-FNAB evaluation after FNAB appears to be more diagnostic than cytology and scintigraphy. Of all the procedures used, PTH-FNAB appears to be the method of choice when the target is US suggestive and reachable. PTH-FNAB appears to be a useful method of guiding surgical intervention.     

Complementary Use of Rasch Models and Nonlinear Principal Components Analysis in the Assessment of the Opinion of Europeans About Utilities

Two non-standard techniques – the Rasch Model and Nonlinear Principal Components Analysis – originally proposed in other fields are presented and discussed to measure the opinion of European citizens about utilities. The Eurobarometer survey data are thus considered. The potential of both methods and their complementary use are highlighted; in particular the methods allow the questionnaire to be calibrated, the role of different services and aspects of service to be established, and the consumer satisfaction to be assessed and compared among European countries, different years and services.     

Rab5 is a signalling GTPase involved in actin remodelling by receptor tyrosine kinases

Rab5 is a small GTPase involved in the control of intracellular trafficking, both at the level of receptor endocytosis and endosomal dynamics. The finding that Rab5 can be activated by receptor tyrosine kinases (RTK) raised the question of whether it also participates in effector pathways emanating from these receptors. Here we show that Rab5 is indispensable for a form of RTK-induced actin remodelling, called circular ruffling. Three independent signals, originating from Rab5, phosphatidylinositol-3-OH kinase and Rac, respectively, are simultaneously required for the induction of circular ruffles. Rab5 signals to the actin cytoskeleton through RN-tre, a previously identified Rab5-specific GTPase-activating protein (GAP). Here we demonstrate that RN-tre has the dual function of Rab5-GAP and Rab5 effector. We also show that RN-tre is critical for macropinocytosis, a process previously connected to the formation of circular ruffles. Finally, RN-tre interacts with both F-actin and actinin-4, an F-actin bundling protein. We propose that RN-tre establishes a three-pronged connection with Rab5, F-actin and actinin-4. This may aid crosslinking of actin fibres into actin networks at the plasma membrane. Thus, we have shown that Rab5 is a signalling GTPase and have elucidated the major molecular elements of its downstream pathway.     

The role of increasing temperature variability in European summer heatwaves

Instrumental observations and reconstructions of global and hemispheric temperature evolution reveal a pronounced warming during the past approximately 150 years. One expression of this warming is the observed increase in the occurrence of heatwaves. Conceptually this increase is understood as a shift of the statistical distribution towards warmer temperatures, while changes in the width of the distribution are often considered small. Here we show that this framework fails to explain the record-breaking central European summer temperatures in 2003, although it is consistent with observations from previous years. We find that an event like that of summer 2003 is statistically extremely unlikely, even when the observed warming is taken into account. We propose that a regime with an increased variability of temperatures (in addition to increases in mean temperature) may be able to account for summer 2003. To test this proposal, we simulate possible future European climate with a regional climate model in a scenario with increased atmospheric greenhouse-gas concentrations, and find that temperature variability increases by up to 100%, with maximum changes in central and eastern Europe.